Effects of a novel nonantibiotic macrolide, EM900, on cytokine and mucin gene expression in a human airway epithelial cell line.

Abstract

BACKGROUND/AIMS:

Long-term macrolide therapy is an effective treatment for chronic sinusitis and diffuse panbronchiolitis. However, long-term use of macrolides may promote the growth of drug-resistant bacteria; therefore, development of macrolides with no antibacterial action is desirable. A new erythromycin (EM) derivative, (8R,9S)- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), does not possess antibacterial action.

METHODS:

To determine whether EM900 induced a clinically relevant anti-inflammatory response and repressed mucin gene expression in cells derived from human airway epithelia, we assessed the effects of EM900 on IL-1β-induced inflammatory cytokines in A549 cells and MUC5AC gene expression in HM3-MUC5AC cells. We also investigated the effects of EM900 on IL-1β-induced NF-κB activation. We performed reporter gene assays and quantitative PCR in A549 and HM3-MUC5AC cells.

RESULTS:

Both EM and EM900 suppressed IL-1β-induced IL-8 expression in A549 cells. EM900 also suppressed IL-1β-induced IL-1β and TNF-α expression in A549 cells. EM900 inhibited IL-1β-induced MUC5AC expression in HM3-MUC5AC cells. Both EM and EM900 suppressed IL-1β-induced NF-κB activation in A549 cells.

CONCLUSION:

This study demonstrated that EM900 suppressed the induction of inflammatory cytokines and MUC5AC gene expression in cells derived from human airway epithelia, and our findings indicate that these effects may be mediated by the suppression of NF-κB activation.

• Authors: Kazuya Otsu, Hajime Ishinaga, Shinya Suzuki, Akihiro Sugawara, Toshiaki Sunazuka, Satoshi Omura, Hirofumi Jono, Kazuhiko Takeuchi
• Journal: Pharmacology (Pharmacology) Vol. 88 Issue 5-6 Pg. 327-32 ( 2011) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 22116077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A
• Anti-Inflammatory Agents
• Interleukin-1beta
• Interleukin-8
• MUC5AC protein, human
• Macrolides
• Mucin 5AC
• NF-kappa B
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Erythromycin

Topics

• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Epithelial Cells (drug effects, metabolism)
• Erythromycin (analogs & derivatives, pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• Interleukin-1beta (genetics, pharmacology)
• Interleukin-8 (genetics)
• Macrolides (pharmacology)
• Mucin 5AC (genetics)
• NF-kappa B (metabolism)
• RNA, Messenger (metabolism)
• Tumor Necrosis Factor-alpha (genetics)